Photothermal Treatment of Human Pancreatic Cancer Using PEGylated Multi-Walled Carbon Nanotubes Induces Apoptosis by Triggering Mitochondrial Membrane Depolarization Mechanism

Overview

Journal J Cancer

Specialty Oncology

Date 2014 Sep 27

PMID 25258649

Citations 32

Authors

Teodora Mocan

Cristian T Matea

Iulia Cojocaru

Ioana Ilie

Flaviu A Tabaran

Florin Zaharie

Cornel Iancu

Dana Bartos

Lucian Mocan

Affiliations

Soon will be listed here.

Abstract

Pancreatic cancer (PC) is one of the most lethal solid tumor in humans, with an overall 5-year survival rate of less than 5%. Thermally active carbon nanotubes have already brought to light promising results in PC research and treatment. We report here the construct of a nano-biosystem based on multi-walled carbon nanotubes and polyethylene glycol (PEG) molecules validated through AFM, UV-Vis and DLS. We next studied the photothermal effect of these PEG-ylated multi-walled carbon nanotubes (5, 10 and 50 μg/mL, respectively) on pancreatic cancer cells (PANC-1) and further analyzed the molecular and cellular events involved in cell death occurrence. Using cell proliferation, apoptosis, membrane polarization and oxidative stress assays for ELISA, fluorescence microscopy and flow cytometry we show here that hyperthermia following MWCNTs-PEG laser mediated treatment (808 nm, 2W) leads to mitochondrial membrane depolarization that activates the flux of free radicals within the cell and the oxidative state mediate cellular damage in PC cells via apoptotic pathway. Our results are of decisive importance especially in regard with the development of novel nano-biosystems capable to target mitochondria and to synergically act both as cytotoxic drug as well as thermally active agents in order to overcome one of the most common problem met in oncology, that of intrinsic resistance to chemotherapeutics.

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References

Niu L, Meng L, Lu Q . Folate-conjugated PEG on single walled carbon nanotubes for targeting delivery of Doxorubicin to cancer cells. Macromol Biosci. 2013; 13(6):735-44. DOI: 10.1002/mabi.201200475. View

Toyokuni S . Genotoxicity and carcinogenicity risk of carbon nanotubes. Adv Drug Deliv Rev. 2013; 65(15):2098-110. DOI: 10.1016/j.addr.2013.05.011. View

Iverson N, Barone P, Shandell M, Trudel L, Sen S, Sen F . In vivo biosensing via tissue-localizable near-infrared-fluorescent single-walled carbon nanotubes. Nat Nanotechnol. 2013; 8(11):873-80. PMC: 4066962. DOI: 10.1038/nnano.2013.222. View

Zhou F, Xing D, Wu B, Wu S, Ou Z, Chen W . New insights of transmembranal mechanism and subcellular localization of noncovalently modified single-walled carbon nanotubes. Nano Lett. 2010; 10(5):1677-81. PMC: 6005367. DOI: 10.1021/nl100004m. View

Borja-Cacho D, Jensen E, Saluja A, Buchsbaum D, Vickers S . Molecular targeted therapies for pancreatic cancer. Am J Surg. 2008; 196(3):430-41. PMC: 2570700. DOI: 10.1016/j.amjsurg.2008.04.009. View

Antaris A, Robinson J, Yaghi O, Hong G, Diao S, Luong R . Ultra-low doses of chirality sorted (6,5) carbon nanotubes for simultaneous tumor imaging and photothermal therapy. ACS Nano. 2013; 7(4):3644-52. DOI: 10.1021/nn4006472. View

Das M, Singh R, Datir S, Jain S . Intranuclear drug delivery and effective in vivo cancer therapy via estradiol-PEG-appended multiwalled carbon nanotubes. Mol Pharm. 2013; 10(9):3404-16. DOI: 10.1021/mp4002409. View

Mulvey J, Villa C, McDevitt M, Escorcia F, Casey E, Scheinberg D . Self-assembly of carbon nanotubes and antibodies on tumours for targeted amplified delivery. Nat Nanotechnol. 2013; 8(10):763-71. PMC: 3798027. DOI: 10.1038/nnano.2013.190. View

Huang N, Wang H, Zhao J, Lui H, Korbelik M, Zeng H . Single-wall carbon nanotubes assisted photothermal cancer therapy: animal study with a murine model of squamous cell carcinoma. Lasers Surg Med. 2010; 42(9):638-48. DOI: 10.1002/lsm.20968. View

10.

Song M, Zeng L, Yuan S, Yin J, Wang H, Jiang G . Study of cytotoxic effects of single-walled carbon nanotubes functionalized with different chemical groups on human MCF7 cells. Chemosphere. 2013; 92(5):576-82. DOI: 10.1016/j.chemosphere.2013.03.058. View

11.

Perry S, Norman J, Barbieri J, Brown E, Gelbard H . Mitochondrial membrane potential probes and the proton gradient: a practical usage guide. Biotechniques. 2011; 50(2):98-115. PMC: 3115691. DOI: 10.2144/000113610. View

12.

Mocan L, Ilie I, Tabaran F, Dana B, Zaharie F, Zdrehus C . Surface plasmon resonance-induced photoactivation of gold nanoparticles as mitochondria-targeted therapeutic agents for pancreatic cancer. Expert Opin Ther Targets. 2013; 17(12):1383-93. DOI: 10.1517/14728222.2013.855200. View

13.

Fulda S, Galluzzi L, Kroemer G . Targeting mitochondria for cancer therapy. Nat Rev Drug Discov. 2010; 9(6):447-64. DOI: 10.1038/nrd3137. View

14.

Tu X, Ma Y, Cao Y, Huang J, Zhang M, Zhang Z . PEGylated carbon nanoparticles for efficient in vitro photothermal cancer therapy. J Mater Chem B. 2020; 2(15):2184-2192. DOI: 10.1039/c3tb21750g. View

15.

Boren J, Brindle K . Apoptosis-induced mitochondrial dysfunction causes cytoplasmic lipid droplet formation. Cell Death Differ. 2012; 19(9):1561-70. PMC: 3422477. DOI: 10.1038/cdd.2012.34. View

16.

Mocan L, Tabaran F, Mocan T, Bele C, Orza A, Lucan C . Selective ex-vivo photothermal ablation of human pancreatic cancer with albumin functionalized multiwalled carbon nanotubes. Int J Nanomedicine. 2011; 6:915-28. PMC: 3124855. DOI: 10.2147/IJN.S19013. View

17.

Iancu C, Mocan L, Bele C, Orza A, Tabaran F, Catoi C . Enhanced laser thermal ablation for the in vitro treatment of liver cancer by specific delivery of multiwalled carbon nanotubes functionalized with human serum albumin. Int J Nanomedicine. 2011; 6:129-41. PMC: 3026578. DOI: 10.2147/IJN.S15841. View

18.

Cheng Z, Chai R, Ma P, Dai Y, Kang X, Lian H . Multiwalled carbon nanotubes and NaYF4:Yb3+/Er3+ nanoparticle-doped bilayer hydrogel for concurrent NIR-triggered drug release and up-conversion luminescence tagging. Langmuir. 2013; 29(30):9573-80. DOI: 10.1021/la402036p. View

19.

Moon Y, Lee J, Lee J, Kim T, Kim S . Synthesis of length-controlled aerosol carbon nanotubes and their dispersion stability in aqueous solution. Langmuir. 2009; 25(3):1739-43. DOI: 10.1021/la8031368. View

20.

Smith B, Wepasnick K, Schrote K, Bertele A, Ball W, OMelia C . Colloidal properties of aqueous suspensions of acid-treated, multi-walled carbon nanotubes. Environ Sci Technol. 2009; 43(3):819-25. DOI: 10.1021/es802011e. View